Neurophysiology of Pain in Children with Cerebral Palsy

项目摘要/摘要 脑性瘫痪(CP)是最普遍和最昂贵的儿科神经系统疾病之一，在 美国。尽管这些儿童的脑损伤是非进行性的，但它们经常引发 结构性(即，骨骼排列失调，肌肉痉挛)和功能性(即，共同收缩， 痉挛)肌肉骨骼系统内的异常，在整个发育过程中可能会变得更糟。 这些继发性变化被认为是慢性肌肉骨骼疼痛的主要原因 在脑性瘫痪的儿童中占很大比例。然而，目前在这方面的知识严重不足。 领域，特别是关于持续性疼痛的神经生理机制，因为迄今为止大多数研究 都专注于量化疼痛症状的患病率，而不是潜在的生理学。如果没有这个 关键信息、慢性肌肉骨骼疼痛的预防、治疗和评估将不会取得进展。 我们的广泛脑磁图(MEG)脑成像计划已经确定，早期的大脑侮辱 脑性瘫痪儿童的经历导致躯体感觉对周围感觉的异常处理 皮质。最近，我们扩展了这些结果，显示患有CP的儿童有更多的异常 足部外周刺激后的躯体感觉皮质振荡也有更高的报告疼痛。 这种关系意味着在躯体感觉的完整性之间可能有根本的联系 脑性瘫痪儿童的皮层加工与疼痛知觉。这项提案的目标是测试我们的 科学前提是躯体感觉神经连接紊乱，可能是由于适应不良引起的 脑性瘫痪儿童早期脑损伤后的神经可塑性改变，从而导致 疼痛感知网络和慢性疼痛的活动增加。我们的方法具有“高风险”，但具有 它可能会带来显著的“回报”，因为它可能会带来新的见解和我们理解的范式转变 脑性瘫痪儿童的疼痛感知能力。这项提议的具体目标将：(1)表明 外周刺激大脑皮层机械感受器和伤害性感受器后的躯体感觉皮层振荡 脚和手会随着孩子感觉到的疼痛程度而变化，(2)决定躯体感觉的强度 慢性阻塞性肺疾病儿童在外周刺激后的皮质振荡有不同程度的改变 与高疼痛水平的对比，以及这两组儿童是否与典型发育(TD)儿童不同。简而言之，我们的研究 将使用脑磁图、先进的图像重建方法和时间序列分析来量化 TD儿童刺激外周机械感受器和伤害性感受器后的躯体感觉皮层振荡， 以及患有痉挛双瘫和不同疼痛程度(即严重程度)的儿童。实现我们的目标将提供 对CP儿童慢性疼痛的神经基础有实质性的洞察力，并可能引发 这一人群中肌肉骨骼疼痛的主流治疗和评估。

PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) is one of the most prevalent and costly pediatric neurologic conditions diagnosed in the United States. Although the brain injuries seen in these children are non-progressive, they often instigate a cascade of structural (i.e., boney malalignments, muscular contractures) and functional (i.e., co-contractions, spasticity) abnormalities within the musculoskeletal system that can become worse throughout development. These secondary changes are presumed to be primarily responsible for the chronic musculoskeletal pain that is seen in a large percentage of children with CP. However, currently there is a major lack of knowledge in this area, especially in regard to the neurophysiological mechanisms of the persistent pain, as most studies to date have focused on quantifying the prevalence of pain symptoms and not the underlying physiology. Without this critical information, the prevention, treatment and evaluation of the chronic musculoskeletal pain will not advance. Our extensive magnetoencephalographic (MEG) brain imaging program has identified that the early brain insults experienced by children with CP result in aberrant processing of the peripheral sensations by the somatosensory cortices. Recently, we have extended these results by showing that children with CP who have more abnormal somatosensory cortical oscillations following peripheral stimulation of the feet, also have higher reported pain. This relationship implies that there might be a fundamental link between the integrity of somatosensory cortical processing and the pain perceptions of children with CP. The goal of this proposal is to test our scientific premise that the disturbed somatosensory neural connections, potentially arising from maladaptive neuroplastic changes following early brain injuries, are altered in children with CP and that this leads to heightened activity in the pain perception network and chronic pain. Our approach is of “high risk”, but has the potential to be remarkably “rewarding,” as it may lead to novel insights and a paradigm shift in our understanding of pain perception in children with CP. The Specific Aims of this proposal will (1) demonstrate that the strength of somatosensory cortical oscillations following peripheral stimulation of the mechano- and nociceptors of the feet and hands will scale with a child’s perceived pain levels, and (2) determine if the strength of somatosensory cortical oscillations following peripheral stimulation are differentially altered in children with CP who have low versus high pain levels, and whether both groups differ from typically-developing (TD) children. Briefly, our study will use MEG, advanced image reconstruction methods, and time series analysis to quantify the strength of somatosensory cortical oscillations following stimulation of peripheral mechano- and nociceptors in TD children, and children who have spastic diplegic CP and different pain levels (i.e., severity). Achieving our Aims will provide substantial insight on the neural basis of chronic pain in children with CP, and may spark a paradigm shift in the mainstream treatment and assessment of musculoskeletal pain in this population.